tbuckley/cabot-search huggingface dataset:
Perioperative Gabapentin Linked to Harms for Older Adults
Authors: Anita Slomski
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Patient Characteristics and Postoperative Mortality in Children Undergoing Tonsillectomy—Reply
Authors: M. Bruce Edmonson, David O. Francis, Ryan J. Coller
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Requests for Self-managed Medication Abortion Provided Using Online Telemedicine in 30 US States Before and After the <i>Dobbs v Jackson Women’s Health Organization</i> Decision
Authors: Abigail R. A. Aiken, Jennifer E. Starling, James G. Scott, Rebecca Gomperts
Journal: JAMA (2022)

This study assesses changes in online telemedicine requests to self-manage abortions with medications before vs after the Dobbs v Jackson Women’s Health Organization Supreme Court decision overturning Roe v Wade .
Selpercatinib Receives Regular Approval for Non–Small Cell Lung Cancer
Authors: Howard D. Larkin
Journal: JAMA (2022)

Selpercatinib was granted regular approval from the FDA to treat adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test. A companion diagnostic test also was approved.
New Guidance Aims to Improve Community Access to Naloxone
Authors: Howard D. Larkin
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Challenge of Emergency Abortion Care Following the <i>Dobbs </i>Ruling
Authors: Andrea MacDonald, Hayley B. Gershengorn, Deepshikha Charan Ashana
Journal: JAMA (2022)

This Viewpoint discusses how limited or blocked access to legal abortion will affect the provision of emergency and critical care, including negative effects on patient health, legal intrusion into the patient-physician decision-making process, and concerns about legal jeopardy.
Earlier Bedtimes Help Kids Get More Sleep
Authors: Anita Slomski
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Epidemiology and Therapeutic Strategies for Women With Preexisting Diabetes in Pregnancy: How Far Have We Come? The 2021 Norbert Freinkel Award Lecture
Authors: Denice S. Feig
Journal: Diabetes Care (2022)

The field of diabetes in pregnancy has witnessed tremendous changes over the past 30 years, with an explosive growth in case numbers along with new and exciting opportunities to affect outcomes. Type 1 diabetes in pregnancy has increased by 40%, but type 2 diabetes in pregnancy, rarely seen 30 years ago, has more than doubled and, in some cases, tripled in prevalence. Compared with women with type 2 diabetes, women with type 1 diabetes have higher HbA1c, more large-for-gestational-age infants, and more preterm births. Women with type 2 diabetes have more chronic hypertension, more socioeconomic deprivation, and higher rates of perinatal mortality. Large randomized trials in women with diabetes in pregnancy have helped us understand the effectiveness of new technologies (i.e., continuous glucose monitoring) in women with type 1 diabetes, and the addition of metformin to insulin in women with type 2 diabetes, in improving pregnancy outcomes. Future endeavors, including artificial pancreas systems in women with type 1 diabetes and the use of continuous glucose monitoring, a better understanding of nutrition during pregnancy, and approaches to improve preconception and pregnancy self-care in women with type 2 diabetes, may lead to further improved outcomes.
Long-term Effect of Lifestyle Interventions on the Cardiovascular and All-Cause Mortality of Subjects With Prediabetes and Type 2 Diabetes: A Systematic Review and Meta-analysis
Authors: Kelly P. Zucatti, Paula P. Teixeira, Laura F. Wayerbacher, Giovana F. Piccoli, Poliana E. Correia, Natasha K.O. Fonseca, Karla S. Moresco, Bruno A. Guerra, Michelle G. Maduré, Laura P. Farenzena, Anize D. Frankenberg, Elisa Brietzke, Bruno Halpern, Oscar Franco, Verônica Colpani, Fernando Gerchman
Journal: Diabetes Care (2022)

BACKGROUND Lifestyle interventions improve the metabolic control of individuals with hyperglycemia. PURPOSE We aimed to determine the effect of lifestyle interventions on cardiovascular and all-cause mortality in this population. DATA SOURCES Searches were made through MEDLINE, Cochrane CENTRAL, Embase, and Web of Science (no date/language restriction, until 15 May 2022). STUDY SELECTION We included randomized clinical trials (RCTs) of subjects with prediabetes and type 2 diabetes, comparing intensive lifestyle interventions with usual care, with a minimum of 2 years of active intervention. DATA EXTRACTION Data from the 11 RCTs selected were extracted in duplicate. A frequentist and arm-based meta-analysis was performed with random-effects models to estimate relative risk (RR) for mortality, and heterogeneity was assessed through I2 metrics. A generalized linear mixed model (GLMM) was used to confirm the findings. DATA SYNTHESIS Lifestyle interventions were not superior to usual care in reducing cardiovascular (RR 0.99; 95% CI 0.79–1.23) or all-cause (RR 0.93; 95% CI 0.85–1.03) mortality. Subgroup, sensitivity, and meta-regression analyses showed no influence of type of intervention, mean follow-up, age, glycemic status, geographical location, risk of bias, or weight change. All of these results were confirmed with the GLMM. Most studies had a low risk of bias according to the RoB 2.0 tool and the certainty of evidence was moderate for both outcomes. LIMITATIONS Most studies had a low risk of bias according to the RoB 2.0 tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach resulted in moderate certainty of evidence for both outcomes. Differences in lifestyle programs and in usual care between the studies should be considered in the interpretation of our results. CONCLUSIONS Intensive lifestyle interventions implemented so far did not show superiority to usual care in reducing cardiovascular or all-cause mortality for subjects with prediabetes and type 2 diabetes.
Extracellular vesicles in the pathogenesis and treatment of acute lung injury
Authors: Qian Hu, Shu Zhang, Yue Yang, Jia-Qi Yao, Wen-Fu Tang, Christopher J. Lyon, Tony Ye Hu, Mei-Hua Wan
Journal: Military Medical Research (2022)

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common life-threatening lung diseases associated with acute and severe inflammation. Both have high mortality rates, and despite decades of research on clinical ALI/ARDS, there are no effective therapeutic strategies. Disruption of alveolar-capillary barrier integrity or activation of inflammatory responses leads to lung inflammation and injury. Recently, studies on the role of extracellular vesicles (EVs) in regulating normal and pathophysiologic cell activities, including inflammation and injury responses, have attracted attention. Injured and dysfunctional cells often secrete EVs into serum or bronchoalveolar lavage fluid with altered cargoes, which can be used to diagnose and predict the development of ALI/ARDS. EVs secreted by mesenchymal stem cells can also attenuate inflammatory reactions associated with cell dysfunction and injury to preserve or restore cell function, and thereby promote cell proliferation and tissue regeneration. This review focuses on the roles of EVs in the pathogenesis of pulmonary inflammation, particularly ALI/ARDS.
MiR-125b-5p modulates the function of regulatory T cells in tumor microenvironment by targeting TNFR2
Authors: Mengmeng Jiang, Yang Yang, Liling Niu, Ping Li, Yibo Chen, Ping Liao, Yifei Wang, Jingbin Zheng, Fengyang Chen, Huanhuan He, Hui Li, Xin Chen
Journal: Journal for ImmunoTherapy of Cancer (2022)

Tumor necrosis factor receptor type 2 (TNFR2) is primarily expressed by CD4+FoxP3+ regulatory T cells (Tregs), especially those present in tumor microenvironment. There is compelling evidence that TNFR2 plays a crucial role in the activation, expansion, and phenotypic stability of Tregs and promotes tumor immune evasion. Understanding of epigenetic regulation of TNFR2 expression in Tregs may help device a novel strategy in cancer immunotherapy.MiR-125b-5p-overexpressing or knockdown murine CD4 T cells and Tregs were constructed, and the effect of miR-125b-5p on Tregs proliferation, suppressive function and TNFR2 expression were examined. In vivo antitumor efficacy of Ago-125b-5p (miR-125b-5p agomir) was evaluated in MC38 tumor bearing mice, and tumor-infiltrating Tregs and CD8+ cytotoxic T lymphocytes (CTLs) were analyzed. RNA-seq analysis was applied to reveal the genes and signaling pathways regulated by miR-125b-5p in Tregs.In this study, we found that TNFR2 was a direct target of miR-125b-5p. Overexpression of miR-125b-5p decreased the proportion of Tregs and their expression of TNFR2 and consequently inhibited its proliferation and suppressive function by regulating the metabolism-related signaling pathways. Moreover, in colon cancer bearing mice, the administration of Ago-125b-5p markedly inhibited the tumor growth, which was associated with reduction of Tregs and increase of IFNγ+CD8+ T cells in tumor environment. Furthermore, in human colon adenocarcinoma patients, we verified that miR-125b-5p expression was downregulated, and low levels of miR-125b-5p were associated with poor prognosis. Interestingly, the expression of miR-125b-5p and TNFR2 were negatively correlated.Our study for the first time found that the expression of TNFR2 by Tregs was regulated by miR-125b-5p. Our results showed that miR-125b-5p had the capacity to inhibit the expression of TNFR2 and immunosuppressive activity of Tregs and consequently enhanced the antitumor efficacy. This property of miR-125b-5p may be therapeutically harnessed in the treatment of human cancers.
Why I . . . keep animals
Authors: Kathy Oxtoby
Journal: BMJ (2022)

a constant companion who reminds her just how much animals mean to people.Basil, her springer spaniel pup and an unofficial therapy dog, regularly accompanies her on visits to patients at the Williton Community Hospital for stroke rehabilitation and care at the end of life in Somerset, where she works as an associate specialist.She recalls the time when they were both at the bedside of a young mother recovering from a severe stroke: "When I asked her how she was doing, she said, 'Today's a better day because Baz is here.'"
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

a-FR is overexpressed in a variety of solid tumors, including high-grade serous ovarian cancer, triple-negative breast cancer, and non-small cell lung cancer.CT900 is a small molecule thymidylate synthase (TS) inhibitor that binds to and is taken up by a-FR.Banerjee and colleagues report results from the first clinical trial to show reproducible single agent responses caused by a small molecule in a-FRoverexpressing cancers.The toxicity profile did not show classical TS inhibitor toxicity such as myelosuppression suggesting differential a-FR mediated uptake in tumor tissue.This trial is proof of concept for developing a-FR targeting small molecules, which are selectively taken up in a-FR-overexpressing tumors for patient benefit and are an alternate approach to antibody drug conjugates that already target a-FR.
Adaptive single-KIR<sup>+</sup>NKG2C<sup>+</sup>NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia
Authors: Alvaro Haroun-Izquierdo, Marianna Vincenti, Herman Netskar, Hanna van Ooijen, Bin Zhang, Laura Bendzick, Minoru Kanaya, Pouria Momayyezi, Shuo Li, Merete Thune Wiiger, Hanna Julie Hoel, Silje Zandstra Krokeide, Veronika Kremer, Geir Tjonnfjord, Stéphanie Berggren, Kristina Wikström, Pontus Blomberg, Evren Alici, Martin Felices, Björn Önfelt, Petter Höglund, Bahram Valamehr, Hans-Gustaf Ljunggren, Andreas Björklund, Quirin Hammer, Lise Kveberg, Frank Cichocki, Jeffrey S Miller, Karl-Johan Malmberg, Ebba Sohlberg
Journal: Journal for ImmunoTherapy of Cancer (2022)

Natural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML). Current treatments are hampered by variability in NK cell subset responses, a limitation which could be circumvented by specific expansion of highly potent single killer immunoglobulin-like receptor (KIR)+NKG2C+ adaptive NK cells to maximize missing-self reactivity.We developed a GMP-compliant protocol to expand adaptive NK cells from cryopreserved cells derived from select third-party superdonors, that is, donors harboring large adaptive NK cell subsets with desired KIR specificities at baseline. We studied the adaptive state of the cell product (ADAPT-NK) by flow cytometry and mass cytometry as well as cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq). We investigated the functional responses of ADAPT-NK cells against a wide range of tumor target cell lines and primary AML samples using flow cytometry and IncuCyte as well as in a mouse model of AML.ADAPT-NK cells were >90% pure with a homogeneous expression of a single self-HLA specific KIR and expanded a median of 470-fold. The ADAPT-NK cells largely retained their adaptive transcriptional signature with activation of effector programs without signs of exhaustion. ADAPT-NK cells showed high degranulation capacity and efficient killing of HLA-C/KIR mismatched tumor cell lines as well as primary leukemic blasts from AML patients. Finally, the expanded adaptive NK cells had preserved robust antibody-dependent cellular cytotoxicity potential and combination of ADAPT-NK cells with an anti-CD16/IL-15/anti-CD33 tri-specific engager led to near-complete killing of resistant CD45dim blast subtypes.These preclinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population with full missing-self recognition capability.
Deciphering molecular and cellular ex vivo responses to bispecific antibodies PD1-TIM3 and PD1-LAG3 in human tumors
Authors: Marina Natoli, Klas Hatje, Pratiksha Gulati, Fabian Junker, Petra Herzig, Zhiwen Jiang, Iakov I Davydov, Markus Germann, Marta Trüb, Daniel Marbach, Adrian Zwick, Patrick Weber, Stefan Seeber, Mark Wiese, Didier Lardinois, Viola Heinzelmann-Schwarz, Robert Rosenberg, Lothar Tietze, Kirsten D Mertz, Pablo Umaña, Christian Klein, Laura Codarri-Deak, Henry Kao, Alfred Zippelius
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Next-generation cancer immunotherapies are designed to broaden the therapeutic repertoire by targeting new immune checkpoints including lymphocyte-activation gene 3 (LAG-3) and T cell immunoglobulin and mucin-domain containing-3 (TIM-3). Yet, the molecular and cellular mechanisms by which either receptor functions to mediate its inhibitory effects are still poorly understood. Similarly, little is known on the differential effects of dual, compared with single, checkpoint inhibition. Methods We here performed in-depth characterization, including multicolor flow cytometry, single cell RNA sequencing and multiplex supernatant analysis, using tumor single cell suspensions from patients with cancer treated ex vivo with novel bispecific antibodies targeting programmed cell death protein 1 (PD-1) and TIM-3 (PD1-TIM3), PD-1 and LAG-3 (PD1-LAG3), or with anti-PD-1. Results We identified patient samples which were responsive to PD1-TIM3, PD1-LAG3 or anti-PD-1 using an in vitro approach, validated by the analysis of 659 soluble proteins and enrichment for an anti-PD-1 responder signature. We found increased abundance of an activated (HLA-DR + CD25 + GranzymeB + ) CD8 + T cell subset and of proliferating CD8 + T cells, in response to bispecific antibody or anti-PD-1 treatment. Bispecific antibodies, but not anti-PD-1, significantly increased the abundance of a proliferating natural killer cell subset, which exhibited enrichment for a tissue-residency signature. Key phenotypic and transcriptional changes occurred in a PD-1 + CXCL13 + CD4 + T cell subset, in response to all treatments, including increased interleukin-17 secretion and signaling toward plasma cells. Interestingly, LAG-3 protein upregulation was detected as a unique pharmacodynamic effect mediated by PD1-LAG3, but not by PD1-TIM3 or anti-PD-1. Conclusions Our in vitro system reliably assessed responses to bispecific antibodies co-targeting PD-1 together with LAG-3 or TIM-3 using patients’ tumor infiltrating immune cells and revealed transcriptional and phenotypic imprinting by bispecific antibody formats currently tested in early clinical trials.
Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications
Authors: Xinyang Zhong, Xuefeng He, Yaxian Wang, Zijuan Hu, Huixia Huang, Senlin Zhao, Ping Wei, Dawei Li
Journal: Journal of Hematology & Oncology (2022)

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. Countless CRC patients undergo disease progression. As a hallmark of cancer, Warburg effect promotes cancer metastasis and remodels the tumor microenvironment, including promoting angiogenesis, immune suppression, cancer-associated fibroblasts formation and drug resistance. Targeting Warburg metabolism would be a promising method for the treatment of CRC. In this review, we summarize information about the roles of Warburg effect in tumor microenvironment to elucidate the mechanisms governing Warburg effect in CRC and to identify novel targets for therapy.
Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer
Authors: Qing-Fang Han, Wen-Jia Li, Kai-Shun Hu, Jie Gao, Wen-Long Zhai, Jing-Hua Yang, Shui-Jun Zhang
Journal: Molecular Cancer (2022)

Abstract Exosomes are well-known key mediators of intercellular communication and contribute to various physiological and pathological processes. Their biogenesis involves four key steps, including cargo sorting, MVB formation and maturation, transport of MVBs, and MVB fusion with the plasma membrane. Each process is modulated through the competition or coordination of multiple mechanisms, whereby diverse repertoires of molecular cargos are sorted into distinct subpopulations of exosomes, resulting in the high heterogeneity of exosomes. Intriguingly, cancer cells exploit various strategies, such as aberrant gene expression, posttranslational modifications, and altered signaling pathways, to regulate the biogenesis, composition, and eventually functions of exosomes to promote cancer progression. Therefore, exosome biogenesis-targeted therapy is being actively explored. In this review, we systematically summarize recent progress in understanding the machinery of exosome biogenesis and how it is regulated in the context of cancer. In particular, we highlight pharmacological targeting of exosome biogenesis as a promising cancer therapeutic strategy.
Collective action may be the missing link in the UK’s pandemic performance
Authors: Cam Donaldson
Journal: BMJ (2022)

Collective action may be the missing link in the UK's pandemic performance Cam Donaldson Yunus chair and distinguished professor of health economicsAs the UK lurched from lockdowns to restrictions throughout 2020-21, many people will have felt as though little progress was being made in the fight against covid-19.We kept returning to the basic public health interventions that had saved lives-encouraging handwashing, physical distancing, and mask wearing.